Gaston Picchio
Tibotec Inc.
Titusville
NJ, USA
Fax: +1 (609) 730-7513
[email protected]
Prevalence of genotypic and phenotypic susceptibility to
etravirine in US samples received for routine resistance testing
MOPDB105
Gaston Picchio, Johan Vingerhoets, Lotke Tambuyzer, Eoin Coakley, Mojgan Haddad, James Witek
1
2
2
3
3
1
Tibotec Inc., Titusville, NJ, USA; 2Tibotec BVBA, Beerse, Belgium; 3Monogram Biosciences, South San Francisco, CA, USA
1
Abstract
Background
In the Phase III DUET trials of the NNRTI etravirine (ETR;
TMC125), 77.0% and 74.1% of ETR-treated patients with
a Tibotec susceptible ETR weighted genotypic score
(WGS) ≤2 or an Antivirogram® fold-change (FC) ≤3 at
baseline, respectively, achieved <50 HIV RNA copies/mL
at Week 48. The prevalence of ETR susceptibility was
investigated in clinical samples referred for routine
resistance testing using Monogram Biosciences (MGR)
ETR WGS and PhenoSense® assay.
Methods
Fourteen thousand, nine hundred and forty samples
submitted to MGR for routine resistance testing from
June 2008 to June 2009 were analysed. Samples were
defined as NNRTI-resistant if they carried at least
one of the following mutations: A98G, L100I, K101E,
K101P, K103N, K103S, V106A, V106I, Y181x, Y188x,
G190x, P225x, F227x, M230L and P236L, where x
represents any amino acid substitution. MGR’s ETR
WGS consisting of 30 mutations1 was used to define
viral susceptibility to ETR, with a genotypic score ≤3
denoting full susceptibility. Phenotypic susceptibility
to ETR was determined using 2.9 and 10 as low and
high clinical cut-offs (CCOs), respectively. The impact
of K103N on genotypic susceptibility to ETR was also
investigated.
Results
Among 5,482 (36.7%) NNRTI-resistant samples,
67.2% were classified as genotypically susceptible and
76.4% as phenotypically susceptible (median FC 0.9)
to ETR, with 10.7% having FC ≥10. Using Tibotec’s
WGS, 67.5% of NNRTI-resistant samples were ETRsusceptible (WGS ≤2). Among NNRTI-susceptible
samples (n=9,458), 99.5% had ETR FC <2.9 (median
0.8) and 0.5% had FC ≥2.9 and <10 (median 3.5). In
a subset of NNRTI-resistant samples (n=4,514), with
(n=3,598) or without (n=1,884) the K103N mutation,
the proportion of ETR genotypically-susceptible
samples (average median FC 1) was 76.9% and 48.6%,
respectively.
Conclusions
s5SINGDIFFERENTINTERPRETATIONSYSTEMSMOSTSAMPLES
received for resistance testing, with or without
evidence of NNRTI resistance, were susceptible to ETR
Conclusions
Using different interpretation systems, most samples
received for routine resistance testing with or without
evidence of NNRTI resistance were susceptible to ETR.
Among NNRTI-resistant samples, more were ETRsusceptible phenotypically than genotypically, and more
were ETR-susceptible among those with K103N.
s4HElVEMOSTFREQUENT%42MUTATIONSINTHIS
dataset (regardless of WGS) were
– Y181C, V90I, G190A, V106I and P225H
s!MONG..24)RESISTANTSAMPLESMOREWERE%42
susceptible phenotypically than genotypically, and
more were ETR-susceptible among those with K103N
s!MONG..24)SUSCEPTIBLESAMPLESMODESTINCREASES
in ETR FC above the lower CCO were associated
primarily with the presence of mutations at position 138
– however, the majority of samples with an E138A
mutation were phenotypically susceptible to ETR
References
1. Benhamida J, et al. Antivir Ther 2008;13(Suppl. 3). A142.
2. Vingerhoets J, et al. AIDS 2010;24:503–14.
Acknowledgements and disclosures
s 4HEAUTHORSWOULDLIKETOEXPRESSTHEIRGRATITUDETO
– the patients and their families
– the investigators
– the study centre staff
– Virco
– Tibotec clinical trial staff
– Tibotec clinical virology, Biometrics
– Monogram Biosciences
s '0AND*7AREFULLTIMEEMPLOYEESOF4IBOTEC)NC*6AND,4ARE
full-time employees of Tibotec BVBA; EC and MH are full-time
employees of Monogram Biosciences
s %DITORIALSUPPORTWASPROVIDEDBY'ARDINER#ALDWELL
Communications; this support was funded by Tibotec
Presented at the XVIII International AIDS Conference, Vienna, Austria, 18–23 July 2010.
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This poster is available on-line at www.tibotec.com
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